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Grants

KLK4 is a key regulator of the reactive stromal microenvironment in prostate cancer

Prostate cancer cells reside in a complex microenvironment, often referred to as the “reactive” stroma, which is a critical component of prostate cancer initiation and progression. This reactive stromal niche is composed of many different cell types including those called cancer associated fibroblasts, which are different from fibroblasts associated with the normal prostatic glandular structure. These cancer associated fibroblasts play a key role in regulating the tumour microenvironment although the underlying specific mechanisms involved are not yet fully understood. There is also increasing evidence that this niche is a likely key target for new therapeutic approaches.

Based on our exciting new findings that KLK4 can induce a cancer associated fibroblast-like change in prostate fibroblasts, we hypothesise that KLK4 is a critical regulator of the reactive stromal niche and thus a key contributor to prostate cancer initiation and progression.

This project involves comprehensive high throughput gene and protein analyses, coupled with three dimensional laboratory models that mimic this complex tumour microenvironment and validation in vivo to determine the functional consequences of KLK4 action on both prostate cancer cells and their surrounding stromal fibroblasts.

The data derived from this research will provide key information that will determine the potential of KLK4 as a therapeutic target or prognostic biomarker for disrupting the reactive stromal niche and thus provide a novel therapeutic approach for prostate cancer.

Investigators

Judith Clements APCRC-Q, IHBI, QUT, TRI

Associate Investigators

Colleen Nelson APCRC-Q, IHBI, QUT, TRI
Gail Risbridger Monash University
Jeffrey Gorman IHBI, QUT
Joanne Perry-Keene
Jonathon Harris IHBI, QUT
Melanie Lehman APCRC-Q, IHBI, QUT, TRI
Oded Kleifeld Monash University
Renea Taylor Monash University

Duration

2014 - 2015

Funding

Cancer Council Queensland $200 000